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our discussion and attention, and we are ultimate- ly in charge of our own destiny.
insult/injury Health
HEALTHY BASELINE
Disease Health
DISEASED BASELINE
Disease treatment TIME
The apocalyptic horsemen of the pharma industry
The following areas represent a rather familiar set of issues inherent to pharmaceutical R&D efforts and issues that are taught to students at very early educational times. Their description is not meant to offend any intellect, but to highlight salient points that may have been forgotten or ‘sent to pasture’ because of their simplistic and fundamen- tal nature. Their importance, however, cannot be underscored and they represent not only the har- bingers of our own world but, perhaps, the means to create a world more paradisiacal than the cur- rent one.
Horseman #1: Homeostasis Figure 1
Homeostasis: The propensity of most biological systems to return to a pre-set value,
regardless if baseline is one of health (upper section) or disease (lower section). For example, when a healthy person is exposed to an insult or injury (maroon arrow) the deviation towards ‘disease’ is reversed over time;
importantly, too, even if subsequent insults/injuries
continue (green arrows). The ultimate return to ‘health’ may not occur fully but the
propensity to return to the healthy baseline fortunately
exists. Unfortunately, a similar propensity exists for systems in a diseased baseline state
such that treatments (singly or over time) will be fought by the system
decades. And if these basics are brought back to the forefront of our discussions, perhaps it may be appropriate to begin asking if there needs to be more radical shifts in our worldview and practices in order to get us to a new world only dreamt of before.
The utility of myth, metaphor and allegory Myths, metaphors and allegories are simply means to help frame the discussion of certain topics, and to help them be understood in ways that are mean- ingful as well as transcendental (beyond the specif- ic topic at hand)7. A rather well-known story of the Four Horsemen of the Apocalypse will be adopted for the current perspective. The broadest sense of the apocalyptic story revolves around the end of the previous (historical) world, the ‘battle’ of the components of the current story and the ulti- mate establishment of a new world order. The four horsemen are harbingers (omens) sent to set a divine apocalypse upon the world, serving as vital links between the old and new worlds8. The myth/allegory approach also allows us to frame the discussion points in ways slightly different than in typical scientific discourse, an approach congruent with the thought that: “We can’t solve problems by using the same kind of thinking we used when we created them” (Albert Einstein).
The timelines (pre- versus post-apocalypse), the players (horsemen) and the outcome (a new way of working) in the final judgment story can be applied here with a major exception: the current apocalyp- tic horsemen represent distinct areas amenable to
10
Homeostasis is the propensity of any biological sys- tem to maintain its current state, regardless if this state is healthy, predisposed to disease or acutely or chronically diseased. Moreover, homeostasis must be thought of as a non-static integral: biological sta- tus as a function of time. In a ‘healthy’ person, this is a continued and predictable trajectory of their biological system. A person in a ‘prediseased’ state is healthy but on a trajectory heading toward dis- ease, while a diseased person has exceeded a certain threshold. All of these populations, however, have an established ‘homeostatic set point.’ Biological systems are designed by nature to fight pressures to change from their homeostatic set point (whatever the current set point is) and will recruit massively redundant systems to thwart any deviations greater than normal background variations. Importantly, homeostasis helps a healthy system to be healthy just as much as it does a diseased system to be dis- eased. ‘Resetting the homeostatic bar’ is the ulti- mate end-goal of disease mitigation, so biological systems must be completely reprogrammed if long- term changes are to ever be realised; treatment of symptoms, therefore, will fail unconditionally in the end. An additional but critical point to keep in mind is that human health and disease in developed countries are, metaphorically, ‘already at war’ with their environment, ie our physiological and genetic make-up are evolutionarily hundreds of thousands of years old, but we have been living in ‘non-native’ environments for generations, being exposed to ‘non-native’ pathogens or removing pathogens from our evolutionarily ‘native’ environment, and are living in altered diurnal and seasonal light/dark cycles due to artificial lighting, eg9,10. Even when we are ‘healthy’ we are, in effect, already living in
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